The fundamental question underlying memory function is how information is represented in the brain. Current models suggest that the content of our experiences might be represented by anatomically distinct brain structures, and the nature of those representations might change as they are transformed from novel information to stored memories. Although the central role of the medial temporal lobe (MTL) in episodic memory-memory for individual events-is well established, the nature of content representation in the MTL is still unclear. The anatomical organization of the MTL suggests that individual MTL subregions make unique contributions to the encoding of episodic memories based on content. However, evidence for these distinctions has been mixed. This research proposal will combine high-resolution functional magnetic resonance imaging (fMRI) and high-dimensional analyses to reveal the MTL subregional contributions to content-sensitive encoding with greater precision than previously possible. Experiment 1 will test the hypothesis that MTL cortical subregions and hippocampus make unique responses to different forms of content to support item- level encoding. A novel multivariate analytical technique will allow us to assess the information carried by subthreshold activity. It will also reveal the developing nature of content representations as they are successfully encoded. Experiment 2 will test the hypothesis that specific categories of content representation are reinstated to support memory for episodic details. We will also consider the responses of hippocampal subfields to determine their computational role in mediating encoding and reinstatement. Experiment 3 will test the hypothesis that content representations are reactivated to help anticipate the future. Multivariate analysis of patterned activation during timepoints before expected events will test whether they carry information predicting the content of those events. This research will help identify the nature of content representation in the MTL, giving us a clearer picture of how we remember the world around us. It will also give us insight into the possible functional role of content codes in MTL. Understanding these open questions through the completion of the proposed project will help us identify the underlying nature of impairment from conditions that affect MTL function or structure, including Alzheimer's disease, post-traumatic stress disorder, and schizophrenia. ) PUBLIC HEALTH RELEVANCE: The proposed research investigates how medial temporal lobe structures support memory for the content of experienced events. It will also reveal how our memories are reactivated to make sense of current events or predict the future. Understanding these mechanisms will help us identify the underlying nature of impairment from conditions that affect MTL function or structure, including Alzheimer's disease, post-traumatic stress disorder, and schizophrenia.)